Human iPSC-derived heart organoids modeling the etiology of pregestational diabetes induced congenital heart defects
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE201343 | GEO | 2023/08/07
REPOSITORIES: GEO
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Project description:Human iPSC-derived heart organoids modeling the etiology of pregestational diabetes induced congenital heart defects
| PRJNA830899 | ENA
Project description:Congenital heart disease (CHD) is the most frequent birth defect and affects nearly 1% of newborns. The etiology of CHD is largely unknown and only a small percentage can be assigned to environmental risk factors such as maternal diseases or exposure to mutagenic agents during pregnancy. Chromosomal imbalances have been identified in many forms of syndromic CHD, but next to nothing is known about the impact of DNA copy number changes in non-syndromic CHD. Here we present a sub-megabase resolution array CGH screen of a cohort with CHD as the sole abnormality at the time of diagnosis. Keywords: array CGH In this BAC array CGH study 104 patients with congenital heart disease and some of their parents were screened for DNA copy number changes at submegabase resolution. No dye swap was performed.
2008-05-11 | E-GEOD-7527 | biostudies-arrayexpress
Project description:Hypoplastic left heart syndrome (HLHS) is a heterogeneous, lethal combination of congenital malformations that result in a heart unable to sustain systemic circulation. The genetic determinants of this disorder are largely unknown. Evidence of copy number variants (CNVs) contributing to the genetic etiology of HLHS and other congenital heart defects (CHDs) has been mounting. However, the functional effects of such CNVs have not been examined, particularly in cases where the variant of interest is found in only a single patient. Initially whole-genome SNP microarrays were employed to detect CNVs in two patient cohorts (N = 70 total) predominantly diagnosed with some form of nonsyndromic HLHS. We discovered 16 rare variants adjacent to or overlapping 20 genes associated with cardiovascular or premature lethality phenotypes in mouse knockout models. Fifteen of the 16 variants were identified in separate patients, suggestive of a private mutation model of disease. We evaluated the impact of selected variants on the expression of nine of these genes through quantitative PCR on cDNA derived from patient heart tissue. Four genes displayed significantly altered expression in patients with an overlapping or proximal CNV verses patients without such CNVs. Thus, rare and private genomic imbalances perturb transcription of genes affecting cardiogenesis in a subset of nonsyndromic HLHS patients. Some of these genes influence extracellular matrix structure, cardiac neural crest development, and coronary vascularization. A total of 70 samples from CHD patients, mostly with nonsyndromic HLHS, yielded SNP genotypes and probe intensity ratios of sufficient quality for CNV identification. Two classes of CNV detection algorithms (HMM and CBS) were employed. After identification, concordant entries were subjected to selection criteria based on rarity and gene content, which produced putative candidate genes for follow-up experiments.
2015-12-10 | E-GEOD-66032 | biostudies-arrayexpress
Project description:Maternal pregestational diabetes (PGDM) is a risk factor for development of congenital heart defects (CHDs). Glycemic control before pregnancy reduces the risk of CHDs. A meta-analysis was used to estimate summary ORs and mathematical modeling was used to estimate population attributable fractions (PAFs) and the annual number of CHDs in the U.S. potentially preventable by establishing glycemic control before pregnancy.A systematic search of the literature through December 2012 was conducted in 2012 and 2013. Case-control or cohort studies were included. Data were abstracted from 12 studies for a meta-analysis of all CHDs.Summary estimates of the association between PGDM and CHDs and 95% credible intervals (95% CrIs) were developed using Bayesian random-effects meta-analyses for all CHDs and specific CHD subtypes. Posterior estimates of this association were combined with estimates of CHD prevalence to produce estimates of PAFs and annual prevented cases. Ninety-five percent uncertainty intervals (95% UIs) for estimates of the annual number of preventable cases were developed using Monte Carlo simulation. Analyses were conducted in 2013. The summary OR estimate for the association between PGDM and CHDs was 3.8 (95% CrI=3.0, 4.9). Approximately 2670 (95% UI=1795, 3795) cases of CHDs could potentially be prevented annually if all women in the U.S. with PGDM achieved glycemic control before pregnancy.Estimates from this analysis suggest that preconception care of women with PGDM could have a measureable impact by reducing the number of infants born with CHDs.
| S-EPMC4455032 | biostudies-literature
Project description:Kids First: Congenital Heart Defects and Laterality Birth Defects
| PRJNA760554 | ENA
Project description:Kids First: Congenital Heart Defects and Laterality Birth Defects
| PRJNA760555 | ENA
Project description:Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines. In this study, we want to identify genes and pathways specifically dysregulated in atrioventricular septal defect and /or atrial septal defect + ventricular septal defect in case of trisomy 21. Total RNA obtained from DS lymphoblastoid cell lines without congenital heart disease compared to cell lines from DS with congenital heart disease.
2012-08-14 | E-GEOD-34457 | biostudies-arrayexpress
Project description:To identify the molecular causes of heterotaxy syndrome patients with congenital heart defects, an Affymetrix CytoScan HD array was used to identify possible pathogenic CNVs in 63 patients. A total of 59 samples passed initial quality control.
2018-05-24 | E-MTAB-6820 | biostudies-arrayexpress
Project description:Hypoplastic left heart syndrome (HLHS) is a heterogeneous, lethal combination of congenital malformations that result in a heart unable to sustain systemic circulation. The genetic determinants of this disorder are largely unknown. Evidence of copy number variants (CNVs) contributing to the genetic etiology of HLHS and other congenital heart defects (CHDs) has been mounting. However, the functional effects of such CNVs have not been examined, particularly in cases where the variant of interest is found in only a single patient. Initially whole-genome SNP microarrays were employed to detect CNVs in two patient cohorts (N = 70 total) predominantly diagnosed with some form of nonsyndromic HLHS. We discovered 16 rare variants adjacent to or overlapping 20 genes associated with cardiovascular or premature lethality phenotypes in mouse knockout models. Fifteen of the 16 variants were identified in separate patients, suggestive of a private mutation model of disease. We evaluated the impact of selected variants on the expression of nine of these genes through quantitative PCR on cDNA derived from patient heart tissue. Four genes displayed significantly altered expression in patients with an overlapping or proximal CNV verses patients without such CNVs. Thus, rare and private genomic imbalances perturb transcription of genes affecting cardiogenesis in a subset of nonsyndromic HLHS patients. Some of these genes influence extracellular matrix structure, cardiac neural crest development, and coronary vascularization.
2015-12-10 | GSE66032 | GEO
Project description:Congenital heart disease (CHD) is the most frequent birth defect and affects nearly 1% of newborns. The etiology of CHD is largely unknown and only a small percentage can be assigned to environmental risk factors such as maternal diseases or exposure to mutagenic agents during pregnancy. Chromosomal imbalances have been identified in many forms of syndromic CHD, but next to nothing is known about the impact of DNA copy number changes in non-syndromic CHD. Here we present a sub-megabase resolution array CGH screen of a cohort with CHD as the sole abnormality at the time of diagnosis. Keywords: array CGH
2008-05-12 | GSE7527 | GEO